Human Fetal and Cord Serum Thyroid Hormones: Developmental Trends and Interrelationships

Abstract

Thyroid hormone is essential for fetal and neonatal development in particular of the brain, but little is known about regulation of fetal thyroid hormone levels throughout human gestation. The purpose of this study was to clarify developmental trends and interrelationships among T(4), free T(4) (FT4), thyroxine-binding globulin (TBG), TSH, T(3), rT(3), and T(4) sulfate (T4S) levels in cord and fetal blood sera (n = 639, 15-42 wk gestation) and correlate infant levels (23-42 wk gestation) to maternal values (n = 428, 16-45 yr) and those of nonpregnant women (n = 233, 16-46 yr). In cord and fetal serum, T(4), T(3), and TBG levels increase with gestation until term; TSH, FT4, T4S, and rT(3) levels increase and peak in the late second/early third trimester and then decline to term; T(4)/TBG ratios increase until late second trimester and plateau to term. Term cord sera TSH, TBG, and all iodothyronine levels, except T(3), are higher than nonpregnant women. In the third trimester, cord serum FT4, TSH, rT(3), and T4S levels are also higher than corresponding maternal levels, but T(4), T(3), and TBG levels are lower than maternal values. The late second/early third trimester is a critical transition period in fetal thyroid hormone metabolism, which may be interrupted by preterm birth and contribute to postnatal thyroid dysfunction.

Expression of thyroid hormone transporters in the human placenta and changes associated with intrauterine growth restriction

“…Since the fetal circulating TH concentration and fetal brain TH content is closely correlated to maternal free T4 rather than free T3, free T4 is believed to be the major form of TH transported across the placenta [3]. During pregnancy maternal free T4 levels fluctuate between 13.5 to 17.5 pmol/l [45]. Fetal free T4 levels reach 350 approximately 40-50% of maternal concentrations by the early 2 nd trimester [6] and peak in the early 3 rd trimester to 19.3 pmol/L and remain at levels above corresponding maternal concentrations [45].…”

“…During pregnancy maternal free T4 levels fluctuate between 13.5 to 17.5 pmol/l [45]. Fetal free T4 levels reach 350 approximately 40-50% of maternal concentrations by the early 2 nd trimester [6] and peak in the early 3 rd trimester to 19.3 pmol/L and remain at levels above corresponding maternal concentrations [45]. Although, maternal and fetal free T4 concentrations are well below the Km values of all the TH transporters, the relatively lower Km for TH compared to the other compounds transported by the TH transporters (Table 1) should help TH to compete 355 favourably.…”

Thyroid stimulating hormone (TSH) ≥2.5 mU/l in early pregnancy: Prevalence and subsequent outcomes

“…A number of factors contribute, including increased thyroid binding globulin levels, 1 the interaction of human chorionic gonadotrophin (β-hCG) with thyroid stimulating hormone (TSH), 2 placental deiodinase activity, and altered urinary iodine excretion. 3 Although the foetus can concentrate iodine and synthesise thyroid hormone from [10][11][12] weeks, 4 it is mainly reliant upon the transfer of maternal thyroid hormone until approximately 20 weeks of gestation.…”

Nadczynność tarczycy w ciąży — rola oznaczania przeciwciał przeciwko receptorowi TSH i ultrasonograficznego monitorowania płodu

“…Reference ranges for the analysed parameters were as follows: TSH 0.4-4.0 mIU/mL, fT4 10.4-24.4 pmol/L, fT3 1.8-4.2 pg/mL, TPOAbs < 35 IU/mL, TGAbs < 40 IU/mL, TRAbs < 1.8 IU/mL. Normal foetal values for TSH, fT4, fT3, according to gestational age, were described by Hume and Guibourdenche [36,37]. Neonatal TSH values for the Polish population, obtained in driedspot tests, were as follows: median TSH concentration 1.45 mIU/L, 23.5% TSH results ≤ 0.5 mIU/L, 95% TSH results ≤ 5 mIU/L, and 0.2% abnormal measurements > 12.0 mIU/L [38].…”